The immediate objective of the proposed investigation is to ascertain whether urine contains a factor(s) which serves as a promoting agent(s) in urinary bladder neoplasia. Our studies are based on the hypothesis that urine may contain minute amounts of carcinogen(s) derived from either exogenous or endogenous sources and that these induce cancer only when they are present in sufficiently high concentration or act in concert with a second substance in urine which may serve as a co-carcinogen or as a promoter. Available evidence indicates that the urine contains a number of substances which are known to stimulate cell growth, and it is conceivable that some of them may play the role of either tumor promoter or co-carcinogen. The proposed investigation is intended 1) to study the role of urine, specifically its possible role as a co-carcinogen and/or a promoter - as a study model, heterotopically transplanted bladders (HTB) of rats diverted from urine flow will be used; 2) to study the role of urinary constituents as possible co-carcinogens and/or promoters - the substances to be tested will be epidermal growth factor and polyamines; and 3) to test suspected proximate carcinogens using HTBs as a model.